• Korean Journal of Clinical Pharmacy
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• v.30 no.1
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• pp.36-43
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• 2020

Background: Tacrolimus, a calcineurin inhibitor, is an immunosuppressant used in post-transplantation maintenance therapy. The drug has a narrow therapeutic range and requires periodic therapeutic drug monitoring. Although many studies have reported the effects of intrapatient variability of tacrolimus on survival, rejection, and complications in renal transplant recipients, very few studies have reported these effects in liver transplant recipients. The purpose of this study was to evaluate the effect of intrapatient variability of tacrolimus on clinical outcomes after liver transplantation. Methods: Intrapatient variability was calculated using individual, averaged tacrolimus concentrations. Patients were divided into two groups according to their median variability value: high-variability and low-variability groups. The rate of deviation from the therapeutic range, incidence of acute rejection, post-transplant diabetes, incidence of infection, and estimated glomerular filtration rate (eGFR) after transplantation were compared between the groups. Results: Of the total patients (n=82), the high-variability group (n=41) exhibited significantly greater deviation from the therapeutic range (65.92% vs. 56.84%; p<0.001). There was no significant difference in acute rejection or post-transplantation diabetes incidence or eGFR; however, the number of infection in the first 6 months was significantly lower in the low-variability group (0.4 vs. 0.9 times; p=0.039). Multiple linear regression analysis showed that the number of infection significantly increased as intrapatient variability increased (p=0.015). Conclusion: High intrapatient variability in tacrolimus concentrations was strongly associated with an increased frequency of deviation from the suggested therapeutic range and an increased number of infection.

• Journal of Radiopharmaceuticals and Molecular Probes
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• v.5 no.2
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• pp.89-100
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• 2019

In our previous studies, we developed a ¹⁸F-labeled TSPO-binding ligand, named [¹⁸F]CB251, which has been proved to be a promising TSPO-binding PET radiotracer for the detection and monitoring of TSPO expression in pathological diseases. (Ki = 0.27 nM for TSPO, 1.96% ID/g of tumor uptake at 1h post-injection) Based on these results, we utilized 6,8-dichloro-2-phenylimidazo[1,2-a]pyridineacetamide analogs, CB185 (1) as a targeting moiety for the selective delivery of probes and anticancer molecules to TSPO-overexpressed tissues. In this study, we designed CB185 derivatives contains different PEG chains (n = 1, 3 and 5) and fluorescence dye (Cy5) to identify the necessary space between a TSPO-binding ligand and an anticancer agent. Three CB185 derivatives (11a-c) which contains Cy5 and PEG chain, were synthesized and the effect of PEG additive on their TSPO-binding affinities were evaluated using in vitro assays. The binding affinity for compounds 11a-c was lower than that of PK11195 (Ki = 3.2 nM), but still characterized by nanomolar binding affinity for TSPO (Ki = 46.5 nM for 11a, 51.0 nM for 11b, and 388.5 nM for 11c). These results showed that the conjugates are characterized by a moderate binding affinity toward TSPO except for compound 11c, which PEG chain consist of five PEG monomers. Our finding might add useful information to decide the appropriate PET chain length for developing new TSPO-targeting drug carriers.

• Tuberculosis and Respiratory Diseases
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• v.45 no.3
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• pp.546-552
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• 1998

Background: Up to 90% of a theophylline dose is biotransformed, by interaction with one or more the variants of the cytochrome P-450 drug metabolism system. Macrolides affect the elimination of theophylline by influencing on the microsomal enzyme systems. We evaluate the effect of erythromycin and new macrolides on the serum theophylline level and clearance. Method : Subjects consisted of moderate asthmatic patients with normal renal and hepatic functions. All subjects were non-smokers and treated with oral theophylline 400 mg per day. We randomly assigned 53 patients into four groups. Each group was treated with one macrolides, the first group erythromycin(n:19, 500 mg bid), second roxithromycin (n:14. 150 mg bid), third clarithromycin (n:10, 250 mg bid) and fourth azithromycin(n:10, 250 mg bid). We measured the serum theophylline level and clearance at three intervals, at pretreatment, after the first and fourth week after receiving the following macrolides, erythromycin, roxithromycin and clarithromycin. When azithromycin was administered, the serum theophylline level was measured at pretreatment and after one week of treatment They were measured by a computerized program of Bayesian method. Results : When compared with control, erythromycin and roxithromycin-treated groups had a significantly elevated serum theophylline level and decreased clearance. However, there were no significant changes of the serum theophylline level and clearance in clarithromycin and azithromycin-treated groups. Conclusion : These results suggest that theophylline dose may need to be readjusted and have periodic drug monitoring when erythromycin or roxithromycin is administered concurrently.

• Korean Journal of Food Science and Technology
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• v.40 no.1
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• pp.101-105
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• 2008

Enterobacter sakazakii is implicated in severe forms of neonatal infections such as meningitis and sepsis. This organism has been isolated from a wide range of foods, including cheese, vegetables, grains, herbs, and spices, but its primary environment is still unknown. Generally, dried infant milk formula has been epidemiologically identified as the source of E. sakazakii. Sunsik (a powdered mixture of roasted grains and other foodstuffs) is widely consumed in Korea as a side dish or energy supplement. Sunsik is consumed without heat treatment; thus, lacking an additional opportunity to inactivate foodborne pathogens. Therefore, its microbiological safety should be guaranteed. In this study, the prevalence of E. sakazakii was monitored in 23 different sunsik component flours, using FDA recommended methods; but E. sakazakii medium (Neogen) and Chromogenic E. sakazakii medium (Oxoid) were used as the selective media. In total, presumptive E. sakazakii strains were isolated from 8 different sunsik powders. Subsequently, an API 20E test was conducted, and 15 strains from 5 different sunsik flours (sea tangle, brown rice, non-glutinous rice, cheonggukjang, dried anchovy) were confirmed as E. sakazakii. Fifteen strains were again confirmed by PCR amplification, using three different primer sets (tDNA sequence, ITS sequence, 16S rRNA sequence), and compared to ATCC strains (12868, 29004, 29544, 51329). They were once again confirmed by their enzyme production profiles using an API ZYM kit. Finally, RAPD (random amplified polymorphic DNA)-genotyping was carried out as a monitoring tool to determine the contamination route of E. sakazakii during processing.

• The Korean Journal of Pesticide Science
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• v.15 no.4
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• pp.389-400
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• 2011

A high-performance liquid chromatographic (HPLC) method was developed to determine residues of phenothrin and silafluofen, known as synthetic pyrethroids, in agricultural commodities. Insecticide residues were extracted with acetone from representative samples of four crops which comprised rice, apple, pepper and cabbage. The extract was purified serially by liquid-liquid partition and Florisil column chromatography. For rice and pepper samples, acetonitrile/n-hexane partition was additionally adopted to remove nonpolar interferences. Reversed phase HPLC using an octadecylsilyl column was successfully applied to separate two phenothrin isomers and silafluofen from sample co-extractives. Intact parent compounds were sensitively detected by ultraviolet absorption at 226 nm. Recovery experiment at the quantitation limit validated that the proposed method could apparently determine phenothrin and silafluofen residues at 0.02 and 0.01 mg/kg, respectively. Mean recoveries of phenothrin and silafluofen from four crop samples fortified at three levels in triplicate were in the range of 82.4~109.8% and 83.7~109.8%, respectively. Relative standard deviations of the analytical method were all less than 10%, irrespective of crop types and spiking levels. A selected-ion monitoring (SIM) LC/mass spectrometry (MS) with electrospray ionization was provided to confirm the suspected residue of phenothrin, even though no sufficient ionization of silafluofen was obtained. Both phenothrin and silafluofen could be successfully confirmed by gas chromatography/MS SIM with electron impact at 70 eV. The proposed method is sensitive, repeatable and rapid enough to apply to officially routine inspection of agricultural products.

• Parasites, Hosts and Diseases
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• v.53 no.5
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• pp.535-543
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• 2015

Integrated control strategies are important for sustainable control of schistosomiasis and soil-transmitted helminthiasis, despite their challenges for their effective implementation. With the support of Good Neighbors International in collaboration with National Institute of Medical Research, Mwanza, Tanzania, integrated control applying mass drug administration (MDA), health education using PHAST, and improved safe water supply has been implemented on Kome Island over 5 years for controlling schistosomiasis and soil-transmitted helminths (STHs). Baseline surveys for schistosomiasis and STHs was conducted before implementation of any integrated control strategies, followed by 4 cross-sectional follow-up surveys on randomly selected samples of schoolchildren and adults in 10 primary schools and 8 villages, respectively, on Kome islands. Those follow-up surveys were conducted for impact evaluation after introduction of control strategies interventions in the study area. Five rounds of MDA have been implemented from 2009 along with PHAST and improved water supply with pumped wells as other control strategies for complementing MDA. A remarkable steady decline of schistosomiasis and STHs was observed from 2009 to 2012 with significant trends in their prevalence decline, and thereafter infection rate has remained at a low sustainable control. By the third follow-up survey in 2012, Schistosoma mansoni infection prevalence was reduced by 90.5% and hookworm by 93.3% among schoolchildren while in adults the corresponding reduction was 83.2% and 56.9%, respectively. Integrated control strategies have successfully reduced S. mansoni and STH infection status to a lower level. This study further suggests that monitoring and evaluation is a crucial component of any large-scale STH and schistosomiasis intervention.

• Journal of Food Hygiene and Safety
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• v.29 no.1
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• pp.16-20
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• 2014

The prevalence of Bacillus cereus was determined in salad and Kimbab obtained from commercial retailers. Among the 100 salad samples analyzed, 54 samples were negative for B. cereus, whereas the bacterial count was < 10 colony forming units (CFU)/g in 8 samples, < 100 CFU/g in 25 samples, < 1,000 CFU/g in 11 samples, and > 1,000 CFU/g in 2 samples. The mean (standard deviation) was 1.18 log CFU/g (${\pm}0.71$ log CFU/g). In Kimbab, B. cereus was isolated from 20 samples; the mean bacterial count was 1.01 log CFU/g (${\pm}0.71$ log CFU/g). On the basis of the monitoring data, a statistical sampling plan was determined with the NEW sampleplan program (ICMSF), which was used as an analytical tool. To identify the most suitable sampling plan, the microbial limits (m, M) and the maximum allowable number of sample units yielding unsatisfactory test results (c) were varied, but the number of samples units, n = 5, was fixed. Sampling plans showing an acceptable probability (Pa) over 0.95 were considered suitable. Two plans (A and B) were finally suggested. Parameters for plan A are n = 5, c = 0, m = 1,000, and M = 10,000 and for plan B are n = 5, c = 2, m = 100, and M = 1,000. Interestingly, the latter plan was identical to the microbial sampling plan used in New Zealand. Thus, it was concluded that the suggested plan can be used as a sampling plan that is in line with international standards.

• Journal of Applied Biological Chemistry
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• v.61 no.4
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• pp.391-395
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• 2018

There is an increasing concern over arsenic (As) contamination of paddy soil and rice with regard to food safety. This study was conducted to investigate total and inorganic As concentration in one hundred husked and polished rice samples collected at the non-contaminated paddy soil in Korea. Arsenic species in rice samples were extracted using 1% nitric acid ($HNO_3$) with a microwave oven and were measured using high performance liquid chromatography coupled with inductively coupled plasma-mass spectrometry. Mean concentrations of total As in husked rice and polished rice were 0.18 and $0.11mg\;kg^{-1}$, respectively. Also, average inorganic As concentrations in husked rice and polished rice were 0.11 and $0.07mg\;kg^{-1}$, respectively. These levels are lower than the standard guideline value 0.35 and $0.2mg\;kg^{-1}$ for inorganic As in husked and polished rice recommended by Codex Committee on Contaminants in Foods and Ministry of Food and Drug Safety, respectively. The mean of the inorganic As ratio for the total amount of As was 0.65 and 0.67 for husked rice and polished rice, respectively, and the range was from 0.08 to 1.0. For health risk assessment, the average value of cancer risk probability was $9.24{\times}10^{-5}$ and ranged from $2.30{\times}10^{-5}$ to $1.90{\times}10^{-5}$. Therefore, human exposure to As through dietary intake of surveyed rice samples might considered to be a low health risk.

• Analytical Science and Technology
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• v.22 no.3
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• pp.201-209
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• 2009

Four heavy metals (Pb, Cd, As, and Hg) in 38 species (total 325 samples) of oriental animality medicines were monitored by inductively coupled plasma-mass spectrometry (ICP-MS) and automatic mercury analyzer (AMA). The detected concentration range of Pb, Cd, As was presented as $0.02{\mu}gkg^{-1}$ $(D.L){\sim}11.29mgkg^{-1}$, $0.01{\mu}gkg^{-1}$ $(D.L){\sim}2.50 mgkg^{-1}$, $0.12{\mu}gkg^{-1}$ $(D.L){\sim}5.27mgkg^{-1}$, respectively. In case of Hg, it the concentration range was $0.01{\sim}77.11mgkg^{-1}$ except one sample which exceeded detection limit. In all samples of Amydae Carapax and Gallnut, it was not detected over the maximum residue limits of metals. Pb is in charge of the greatest portion of contamination in 22 species of animality medicines, and in case of Hg, 54.46% of total samples were over the maximum residue limits. Therefore, environmental levels of Pb and Hg are needed to continue the researches and the studies for tracking pollution source are required.

• Journal of Ginseng Research
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• v.48 no.2
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• pp.149-162
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• 2024

Ginseng, the roots of Panax species, is an important medicinal herb used as a tonic. As ginsenosides are key bioactive components of ginseng, holistic chemical profiling of them has provided many insights into understanding ginseng. Mass spectrometry has been a major methodology for profiling, which has been applied to realize numerous goals in ginseng research, such as the discrimination of different species, geographical origins, and ages, and the monitoring of processing and biotransformation. This review summarizes the various applications of ginsenoside profiling in ginseng research over the last three decades that have contributed to expanding our understanding of ginseng. However, we also note that most of the studies overlooked a crucial factor that influences the levels of ginsenosides: genetic variation. To highlight the effects of genetic variation on the chemical contents, we present our results of untargeted and targeted ginsenoside profiling of different genotypes cultivated under identical conditions, in addition to data regarding genome-level genetic diversity. Additionally, we analyze the other limitations of previous studies, such as imperfect variable control, deficient metadata, and lack of additional effort to validate causation. We conclude that the values of ginsenoside profiling studies can be enhanced by overcoming such limitations, as well as by integrating with other -omics techniques.